Lung cancer is one of the most common, most lethal, but least treatable diseases. All currently available anticancer drugs are essentially ineffective against most human lung cancers. For the purpose of therapy, lung cancers are generally classified into small cell and non-small cell cancers. With respect to the many different tumor types found in the category of non-small cell cancer, it is difficult to imagine that any one anticancer drug can be effective against all of them. It is the objective of this project to characterize the biology of different types of human lung cancers in vitro by a variety of methods including: scanning and transmission electron microscopy, quantitative image analysis, assays for the activity of a variety of enzymes (e.g., cytochrome P-450, dopa-decarboxylase and production of polypeptide hormones) competence for binding and metabolism of diethylnitrosamine and 4-ipomeanol, and assessment of cytotoxicity of these compounds by colony formation assay and soft agar techniques. We found that established APUD characteristics do not correlate in several small cell cancer lines after priming with 5-hydroxytryptophan (5-HTP) and may hence not be good markers for this category of lung cancer. The small cell cancer lines studied did not bind and metabolize DEN and 4-ipomeanol, and the compounds did not induce cytotoxicity. In contrast, the non-small cell cancer lines selected on the basis of their cell types (as revealed by electron microscopy) exhibited covalent binding, metabolism and cytotoxicity with the 2 compounds, whereby the cell line with morphological features of Clara cells was the most active. These data exemplify that there is a pronounced specificity among different types of lung cancer when it comes to response to chemicals. It may well be possible to take advantage of such specificity for the development of more targeted anticancer drugs.